Vascular Endothelial Growth Factor Receptor Expression as a Prognostic Marker for Survival in Colorectal Cancer

Objective: Vascular endothelial growth factor (VEGF) and its receptors VEGF-R1, -R2 and -R3 play important roles in tumor angiogenesis and are associated with poor prognosis in several solid tumors. However, their functional significance remains unclarified. Here, we investigated the associations between the expression of these receptors and the clinical outcomes of colorectal cancer (CRC) patients. Methods: An immunohistochemical approach was used to detect VEGF-R1, -R2 and -R3 expression in 91 CRC patients who underwent surgery and received chemotherapy at the National Cancer Center Hospital. Statistical analysis was performed to determine the prognostic significance of these biomarkers. Results: Immunoreactivity for VEGF-R2 and -R3 was localized in microvessels and that for VEGF-R1 in cancer cells and stromal microvessels. VEGF-R1 staining in cancer cells (> 10% staining) was found in 84 patients (92%) and in stromal vessels in 75 patients (82%). VEGF-R2 staining in tumor vessels (> 10% staining) was found in 84 patients (92%), whereas VEGF-R3 staining was found in 85 patients (93%). Strong positive staining (> 60% staining) of VEGF-R1 in tumor cells, and VEGF-R1, -R2 and -R3 in vessels was identified in 58 (64%), 33 (36%), 52 (57%) and 60 (66%) patients, respectively. Univariate analysis revealed that VEGF-R1 strong positive staining correlated with shorter post-operative survival in patients with Stage II/III disease (P = 0.01), but neither VEGF-R2 nor R3 expression correlated with survival. Conclusions: VEGF-R1, -R2 and -R3 were highly expressed in CRC cells and stromal vessels. VEGF-R1 strong positive staining correlated with shorter survival after CRC surgery.